Use of dexamethasone may manage Tecvayli’s immune side effect: Study
Steroid shows efficacy for RRMM patients with CRS after immunotherapy
The use of dexamethasone alone may successfully treat the immune side effect cytokine release syndrome (CRS) in people with relapsed or refractory multiple myeloma (RRMM) who are receiving treatment with the approved immunotherapy Tecvayli (teclistamab) and experience mild CRS events, a small study showed.
CRS, a common side effect of certain immunotherapies like Tecvayli, is marked by an aggressive immune system response and the excessive release of inflammatory signaling proteins called cytokines. Mild symptoms of this side effect can range from fatigue and muscle pain to nausea and diarrhea.
While current multiple myeloma guidelines recommend the anti-inflammatory and immunosuppressive medication tocilizumab for CRS associated with Tecvayli-like therapies, this study found that dexamethasone led to similar outcomes for patients when their use was compared over a two-year period.
These preliminary findings support the use of dexamethasone over tocilizumab for treating Tecvayli-related CRS, which, the researchers noted, may help reduce treatment costs.
Still, “further research with a larger sample size is needed to confirm these findings and elucidate any potential subgroup differences in outcomes of patients with differing disease characteristics,” the researchers wrote.
The study, “Dexamethasone for the management of CRS Related to teclistamab in patients with relapsed/refractory multiple myeloma,” was published as correspondence to the editor of the Blood Cancer Journal.
‘Scarce’ evidence available on use of steroids for CRS events, per researchers
CRS, which also can cause fever, shortness of breath, and low blood pressure, is a common side effect of therapies, such as bispecific T-cell engagers, or TCEs, that modulate the immune system. One such therapy is Tecvayli, which is approved for adults with relapsed or refractory — meaning treatment-resistant — multiple myeloma, known as RRMM for short.
In 2024, the International Myeloma Working Group published guidelines for the use of TCEs in multiple myeloma. The group also recommended treating mild to moderate TCE-related CRS with tocilizumab before anti-inflammatory and immunosuppressive steroids like dexamethasone.
This differed from 2024 expert guidelines for people with B-cell non-Hodgkin lymphomas, another type of blood cancer. Those other guidelines recommend anti-fever medications and dexamethasone before tocilizumab to manage mild to moderate CRS related to TCE use.
While dexamethasone would represent a less expensive approach relative to tocilizumab, “evidence of initial CRS management with steroids is very scarce” in multiple myeloma, the researchers noted.
To learn more, a U.S.-based research team investigated the safety and effectiveness of dexamethasone for managing Tecvayli-related CRS in RRMM patients.
The team retrospectively analyzed data from 243 adults, ages 32-89, with RRMM. All started Tecvayli treatment between 2022 and 2024. Tecvayli was administered as a subcutaneous, or under-the-skin, injection in step-up doses of 0.06 mg/kg and 0.3 mg/kg. Those step-up doses were separated by two to three days, and then followed by weekly doses of 1.5 mg/kg.
At a median follow-up of nearly nine months, two-thirds of the patients had responded to Tecvayli, with 38% achieving a complete response or better, meaning there were no signs of cancer. The patients’ median progression-free survival, or the time they lived without signs of disease worsening, was six months.
Slightly more than half of the patients (55%) experienced CRS, which was most often mild (grade 1; 41%) to moderate (grade 2; 13%) in severity.
Significant savings seen with use of dexamethasone vs. tocilizumab
For CRS management, 31 patients (23%) received dexamethasone alone, while 38 (29%) were treated with tocilizumab alone. A total of 30 patients (23%) received both medications. The remaining patients (25%) received supportive care alone, which involved acetaminophen, oxygen, and/or hydration. Two of the patients who received both medications were added to the dexamethasone alone group.
Most of the 33 patients in the dexamethasone group (85%) had experienced mild CRS. Dexamethasone at 10 mg was used for 73% of CRS events, with doses ranging from 4 mg to 20 mg. One to five doses of dexamethasone were administered to patients, with one dose being enough for most patients, the data showed.
Also, 42% of dexamethasone-treated patients experienced another CRS event after a subsequent Tecvayli dose, but these events were of the same or lower grade and resolved with a median of one additional dexamethasone dose. In the five patients (15%) who required more than two doses, 10 mg of dexamethasone was administered every six hours until CRS resolution, per the researchers.
All patients in the tocilizumab group had experienced mild or moderate CRS, and nearly all (92%) needed only one tocilizumab dose (8 mg/kg).
Although a greater proportion of patients in the dexamethasone group than in the tocilizumab group experienced another CRS after a subsequent Tecvayli dose (42% vs. 16%), there were no significant group differences in terms of CRS duration, Tecvayli dose delays, number of hospital days, or hospital discharge delays, the researchers noted.
Our findings suggest patients experiencing grade 1 CRS with teclistamab may safely be treated with as few as one dexamethasone 10 mg dose as an alternative to management with tocilizumab.
In addition, Tecvayli response rates were comparable between the dexamethasone and tocilizumab groups (73% vs. 74%), with most patients in each group achieving a very good partial response or better.
Median progression-free survival was 6.7 months in the tocilizumab group, but was not reached in the dexamethasone group, meaning that most patients given dexamethasone alone for CRS were still showing no signs of myeloma progression at last follow-up.
There were no reports of treatment-related deaths.
“Our findings suggest patients experiencing grade 1 CRS with teclistamab may safely be treated with as few as one dexamethasone 10 mg dose as an alternative to management with tocilizumab,” the team wrote.
The researchers also noted that 26 of the 44 tocilizumab doses administered were used for mild CRS, representing a cost of $165,724 per event. Replacing tocilizumab with dexamethasone, for $3.13 per 10 mg dose, would have saved $165,642 to treat these same 26 mild events.
“These cost savings are particularly intriguing when considering the median number of hospital days and rate of delayed hospital discharge were similar between the groups,” the researchers wrote, adding that “availability of an oral formulation and ease of use should also be taken into account when considering dexamethasone for CRS treatment.”
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